Modulating astrogliosis after neurotrauma

Abstract

Traumatic injury to the adult central nervous system (CNS) results in a rapid response from resident astrocytes, a process often referred to as reactive astrogliosis or glial scarring. The robust formation of the glial scar and its associated extracellular matrix (ECM) molecules have been suggested to interfere with any subsequent neural repair or CNS axonal regeneration. A series of recent in vivo experiments has demonstrated a distinct inhibitory influence of the glial scar on axonal regeneration. Here we review several experimental strategies designed to elucidate the roles of astrocytes and their associated ECM molecules after CNS damage, including astrocyte ablation techniques, transgenic approaches, and alterations in the deposition of the ECM. In the short term, mediators that modulate the inflammatory mechanisms responsible for eliciting astrogliotic scarring hold strong potential for establishing a favorable environment for neuronal repair. In the future, the conditional (inducible) genetic manipulation of astrocytes holds promise for further increasing our understanding of the functional biology of astrocytes as well as opening new therapeutic windows. Nevertheless, it is most likely that, to obtain long distance axonal regeneration within the injured adult CNS, a combinatorial approach involving different repair strategies, including but not limited to astrogliosis modulation, will be required.